Enhanced presynaptic neurotransmitter release in the anterior cingulate cortex of mice with chronic pain

Ming Gao Zhao, Shanelle W. Ko, LongJun Wu, Hiroki Toyoda, Hui Xu, Jessica Quan, Jianguo Li, Yongheng Jia, Ming Ren, Zao C. Xu, Min Zhuo

Research output: Contribution to journalArticle

132 Citations (Scopus)

Abstract

The anterior cingulate cortex (ACC) is a forebrain structure known for its roles in learning and memory. Recent studies show that painful stimuli activate the prefrontal cortex and that brain chemistry is altered in this area in patients with chronic pain. Components of the CNS that are involved in pain transmission and modulation, from the spinal cord to the ACC, are very plastic and undergo rapid and long-term changes after injury. Patients suffering from chronic pain often complain of memory and concentration difficulties, but little is known about the neural circuitry underlying these deficits. To address this question, we analyzed synaptic transmission in the ACC from mice with chronic pain induced by hindpaw injection of complete Freund's adjuvant (CFA). In vitro whole-cell patch-clamp recordings revealed a significant enhancement in neurotransmitter release probability in ACC synapses from mice with chronic pain. Trace fear memory, which requires sustained attention and the activity of the ACC, was impaired in CFA-injected mice. Using knock-out mice, we found that calmodulin-stimulated adenylyl cyclases, AC1 and/or AC8, were crucial in mediating the long-lasting enhanced presynaptic transmitter release in the ACC of mice with chronic pain. Our findings provide strong evidence that presynaptic alterations caused by peripheral inflammation contribute to memory impairments after injury.

Original languageEnglish (US)
Pages (from-to)8923-8930
Number of pages8
JournalJournal of Neuroscience
Volume26
Issue number35
DOIs
StatePublished - Aug 30 2006
Externally publishedYes

Fingerprint

Gyrus Cinguli
Chronic Pain
Neurotransmitter Agents
Freund's Adjuvant
Brain Chemistry
Wounds and Injuries
Calmodulin
Prosencephalon
Prefrontal Cortex
Adenylyl Cyclases
Knockout Mice
Synaptic Transmission
Synapses
Plastics
Fear
Spinal Cord
Learning
Inflammation
Pain
Injections

Keywords

  • Attention
  • Calmodulin-stimulated adenylyl cyclase
  • Cingulate cortex
  • Inflammation
  • Pain
  • Trace fear memory

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Enhanced presynaptic neurotransmitter release in the anterior cingulate cortex of mice with chronic pain. / Zhao, Ming Gao; Ko, Shanelle W.; Wu, LongJun; Toyoda, Hiroki; Xu, Hui; Quan, Jessica; Li, Jianguo; Jia, Yongheng; Ren, Ming; Xu, Zao C.; Zhuo, Min.

In: Journal of Neuroscience, Vol. 26, No. 35, 30.08.2006, p. 8923-8930.

Research output: Contribution to journalArticle

Zhao, MG, Ko, SW, Wu, L, Toyoda, H, Xu, H, Quan, J, Li, J, Jia, Y, Ren, M, Xu, ZC & Zhuo, M 2006, 'Enhanced presynaptic neurotransmitter release in the anterior cingulate cortex of mice with chronic pain', Journal of Neuroscience, vol. 26, no. 35, pp. 8923-8930. https://doi.org/10.1523/JNEUROSCI.2103-06.2006
Zhao, Ming Gao ; Ko, Shanelle W. ; Wu, LongJun ; Toyoda, Hiroki ; Xu, Hui ; Quan, Jessica ; Li, Jianguo ; Jia, Yongheng ; Ren, Ming ; Xu, Zao C. ; Zhuo, Min. / Enhanced presynaptic neurotransmitter release in the anterior cingulate cortex of mice with chronic pain. In: Journal of Neuroscience. 2006 ; Vol. 26, No. 35. pp. 8923-8930.
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